The long-range goal of this project is to understand the molecular basis of selective ion conduction in potassium channels. A gating-modified version of a Shaker potassium channel from Drosophila melanogaster will be expressed in Xenopus oocytes and studied using electrophysiological techniques. The research focuses on a short segment of the ion channel protein which was recently found to be an integral structural component of the ion conduction pathway. Using site-specific mutagenesis, the pore-forming region of the protein will be altered and the functional consequences studied. Inhibitory ions will be used in conjunction with mutagenesis of the channel to probe the structure of the ion conduction pore. Specific hypotheses about the way-inhibitory and conducting ions may interact with chemical groups in the pore will be tested. This study will lead to a better understanding of the molecular basis of ion selectivity in potassium channels. Because potassium channels are related to the sodium and calcium channels, some of the general principles learned in this study may be applicable to those ion channels as well. Potassium channels are key molecular elements involved in the generation of electrical signals in neurons and other cells. This project is health-related because a better understanding of the structure and function of these membrane proteins may open the way, in the future, to the development of pharmacological agents directed against potassium channels.